An important concept in pathologic aging is that in some individuals muscle strength and exercise endurance are significantly decreased through both quantitative and qualitative changes in muscle tissue. This process, termed sarcopenia, leads to frailty, a syndrome characterized by decreased mobility, weakness, and a very poor prognosis for survival, although the causal pathway for this association is not known. The causes of sarcopenia and why it affects some individuals more than others is not known. This is a complicated scientific question because many factors influence muscle physiology and function, including metabolic, hormonal, environmental, life-style, co-morbid medical problems and their treatments, etc. The National Institute on Aging (NIA) has a long-standing interest in sarcopenia and frailty and has established a number of observational studies aimed at understanding the cause and course of these age-related conditions. It is our goal to try to identify factors involved in the initiation and progression of sarcopenia and frailty, and to develop therapies that can reverse or slow these processes. To identify molecular and genetic changes that are associated with sarcopenia, it is crucial that human muscle biopsy specimens be available for laboratory investigations. Dr. Fenton recently visited the Pennington Biomedical Research Facility learning to perform vastus lateralis muscle biopsies under the tutelage of Dr. Steven Smith, an expert in muscle physiology. This proposal will enable the Clinical Research Branch (CRB) to set up this procedure on the NIA Clinical Research Unit located on the 5th floor at Harbor Hospital, and to hone the practical skills that will be needed for analyzing muscle tissue from individuals in observational and interventional clinical trials. The goal will be to become facile at performing muscle biopsies, collecting, labeling and storing the samples, and to ensure that all equipment and expertise required to efficiently perform the procedure are in place. Up to 200 healthy volunteers will be accrued to the study as described below, however after this the protocol will be kept open for the purpose of training other physicians or nurse practitioners in the biopsy procedure, as well as the collection of muscle material for the various core labs, in order to train and guide the technology involved in processing muscle specimens.